Research ArticleCancer

The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma

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Science Translational Medicine  29 Jul 2020:
Vol. 12, Issue 554, eaaz3339
DOI: 10.1126/scitranslmed.aaz3339

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Fighting multiple myeloma with multitargeted T cells

Adoptive cellular therapies are being developed to treat many types of cancer, including multiple myeloma (MM). Lulla et al. performed a clinical study using T cells expanded in response to MM target antigens. The cells were used as adjuvant therapy or in high-risk patients. Therapy was well tolerated and induced clinical responses in a subset of patients. Examination of T cell clonal expansion and antigen loss in MM cells aided understanding of how the multiantigen-targeted T cells were behaving in patients. This approach, which relies on native T cells and does not require expensive or time-consuming gene editing required for some other types of cellular therapy, warrants further investigation for fighting MM.

Abstract

Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)–specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 × 107 to 2 × 107 cells/m2) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product.

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